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Endothelial cells suppress monocyte activation through secretion of extracellular
vesicles containing antiinflammatory microRNAs
#MMPMID25838349
Njock MS
; Cheng HS
; Dang LT
; Nazari-Jahantigh M
; Lau AC
; Boudreau E
; Roufaiel M
; Cybulsky MI
; Schober A
; Fish JE
Blood
2015[May]; 125
(20
): 3202-12
PMID25838349
show ga
The blood contains high concentrations of circulating extracellular vesicles
(EVs), and their levels and contents are altered in several disease states,
including cardiovascular disease. However, the function of circulating EVs,
especially the microRNAs (miRNAs) that they contain, are poorly understood. We
sought to determine the effect of secreted vesicles produced by quiescent
endothelial cells (ECs) on monocyte inflammatory responses and to assess whether
transfer of microRNAs occurs between these cells. We observed that monocytic
cells cocultured (but not in contact) with ECs were refractory to inflammatory
activation. Further characterization revealed that endothelium-derived EVs
(EC-EVs) suppressed monocyte activation by enhancing immunomodulatory responses
and diminishing proinflammatory responses. EVs isolated from mouse plasma also
suppressed monocyte activation. Importantly, injection of EC-EVs in vivo
repressed monocyte/macrophage activation, confirming our in vitro findings. We
found that several antiinflammatory microRNAs were elevated in EC-EV-treated
monocytes. In particular, miR-10a was transferred to monocytic cells from EC-EVs
and could repress inflammatory signaling through the targeting of several
components of the NF-?B pathway, including IRAK4. Our findings reveal that ECs
secrete EVs that can modulate monocyte activation and suggest that altered EV
secretion and/or microRNA content may affect vascular inflammation in the setting
of cardiovascular disease.
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